Basic Science/Principles Flashcards
1
Q
Antibio for leprosy that works in same way as sulphanomide
A
Dapsone
2
Q
Which antibio inhibits p450 liver enzymes and causes drug interactions/toxicity?
A
Ciprofloaxacin
3
Q
Common combo with sulphonamide
A
Trimethoprim
co-trimoxazole
4
Q
Role of penicillin/beta-lactams
A
Inhibits a transpeptidation reaction involved in peptidoglycan utilization in the cell wall
5
Q
Polymixin action
A
Disrupts bacterial membr in gm-bacteria
6
Q
Ethambol and Isoniazid target … and … of mycolic acid
A
Incorporation and synthesis
7
Q
Macrolide action
A
Binds to P-site, preventing the translocation step of the growing polypeptide chain
8
Q
Clavulanic acid
A
Combo w beta-lactam antibios to inhibit beta-lactamase
9
Q
Atypical pneumonia treatment
A
Azithromycin
10
Q
Sulphonamide action
A
Inhibition of folic acid synthesis by acting as a p-aminobenzoic acid analogue
11
Q
Why is metronidazole for anaerobics?
A
Only active when reduced by anaerobic cell enzymes
12
Q
Why are cephalosporins useful in meningitis?
A
Penetrate blood-brain barrier well
13
Q
Ototoxicity from which drugs?
A
Aminoglycosides e.g. gentamicin
14
Q
Role of albumin
A
Regulates oncotic pressure of blood
15
Q
Nine essential AAs
A
My (methionine) Tall (threonine) Handsome (histidine) Vegan (valine) Friend (phenylalanine) Is (isoleucine) Watering (tryptophan) Kale (lysine) Leaves (leucine)
16
Q
Apolipo spec to chylomicrons
A
Apo B48
17
Q
Where are bile salts formed?
A
Liver
From glycine or taurine
18
Q
Role of NK cells
A
Recognise virus-infected/malignant cells without interacting w thymus
19
Q
Cohort study vs case-control
A
Cohort -
Two groups are selected according to their exposure to a particular agent and followed up to see how many develop a disease or other outcome
Case-control - Compares a group with a disease to a group without, looking at past exposure to a possible causal agent for the condition
20
Q
Immunoglobulin types
A
IgG - phagocytosis of bac/virus, passes to fetal circ
IgA - sweat and tears
IgM - first released
IgD - unknown role, activ B cells
IgE - least common, parasites, hypersensitivity
21
Q
Metformin action
A
Activation of AMP-activated protein kinase (AMPK)
22
Q
Fructose intolerance enzyme
A
Aldolase B
23
Q
Noradrenaline binds to…
A
Alpha 1 receptors
24
Q
Lincomycin action
A
Inhibit protein synthesis
25
Th1 vs Th2
Th1 - cell-mediated
| Th2 - humoral
26
What happens to rate of excretion if you incr conc of drug in plasma kinetcs?
Rate is unchanged
27
Assoc gene in neuroblastoma
N-MYC proto-oncogene
28
Phases of drug metabolism
Phase I: oxidation, reduction, hydrolysis
| Phase II: conjugation
29
What type of receptor do insulin and oestrogen bind to?
Insulin - tyrosine kinase receptor
| Oestrogen - nuclear receptor
30
Down's syndrome characteristics
Single palmar crease, prominent supra-orbital ridge, brush spots, slanted ears and hypotonia
31
Neurotransmitter in pre/post-ganglionic neurones
```
Symp
- pre = ACh
- post = NA
Parasymp
- pre + post = ACh
```
32
Order of potency of agonists in adrenoceptors
- **⍺-adrenoceptor:** noradrenaline > adrenaline > isoprenaline
- **β-adrenoceptor:** isoprenaline > adrenaline > noradrenaline
33
Function of beta adrenoceptor subtypes
b1 - stim ad cyclase - incr HR and contraction force
b2 - "" - relax bronch/vasc SM
a1 - stim phospho C - contract vasc SM
a2 - "" - inhibit NA release
34
Muscarinic cholinoceptor functions
M1 - stim phos C - incr stomahc acid
M2 - inhib ad cyclase, opening of K channels - decr HR
M3 - stim phos C - incr saliva and visc SM contraction in bronch
35
Action of atenolol
Selective competitive B2 antagonist
| angina, HT
36
Salbutamol action
Selective B2 antagonist
| asthma bronchodila
37
Atropine action
Comp antag of musc ACh receptors
| reverse bradycardia after MI and anticholinesterase poisoning
38
How does a G protein work when there's no signalling?
1. Receptor unoccupied
2. ⍺ subunit binding site occupied by GDP
3. Effector is not modulated
39
How does G protein receptor work with signal turning on?
1. Agonist activates receptor, causing a conformational change
2. G protein couples with receptor
3. ⍺ subunit releases GDP and GTP binds in its place (guanine nucleotide exchange)
4. ⍺ subunit dissociates from receptor and β𝛾 dimer
1. ⍺ subunit and β𝛾 dimer are both signaling units
5. ⍺ subunit combines with effector and modifies its activity
6. Agonist may dissociate from receptor but signaling can persist because G protein and receptor are now separate
40
How does G protein receptor work in turning signal off?
1. ⍺ subunit acts as an enzyme - hydrolyses GTP to GDP and Pi (signal is now off)
2. ⍺ subunit recombines with β𝛾 subunit
41
Kinase-linked receptor
Hydrophillic protein mediators in plasma membrane that works in hour timescale
e.g. insulin
42
Nuclear receptor
Hydrophobic signalling molecules e.g. steroid hormones in nucleus/cytoplasm
Ligan-gated trans. factors
43
Driving force for Na (in) and K (out)
Na+ influx = Vm - ENa
| K+ influx = Vm - EK+
44
Phases of membr potential
```
Resting potetial
Depol stimulus to reach threshold
Upstroke to overshoot (depol)
Downstroke (repol) to undershoot (hyperpol)
Resting
```
45
Depol vs repol vs hyperpol
D - opening of Na channels (pos feed)
R - closure of Na, opening of K (neg feed)
H - K remains open
46
WHat is saltatory conduction?
Action potential jumps from one node of Ranvier to the next
47
Pharmacology vs pharmakinetics
- **Pharmacology:** what a drug does to the body
| - **Pharmacokinetics:** what the body does to a drug
48
Potency vs efficacy
- **Potency:** amount of drug required to produce a desired effect
- **Efficacy:** maximum response achievable from drug
49
EC50
Concentration of agonist that elicits half maximal effect
50
Phase 1 vs 2 metabolism
Phase 1: change in the drug by oxidation, reduction or hydrolysis
Phase 2: involve the combination of the drug with one of several polar molecules to form a water-soluble metabolite - conjugation
51
Drug that can go directly to phase 2
Codeine (pharmaco active metabolites)
52
Glucuronidation
- Enzyme - uridine disphosphate-glucoronosyltransferases
| - Cofactor - uridine diphosphate glucuronic acid
53
Definition for fates of drug abs in body
Absorption: drug is absorbed from site of administration, entry into the plasma
Distribution: drug leaves bloodstream and is distributed into interstitial and intracellular fluids
Metabolism: drug transformation by metabolism - liver and other tissues
Excretion: drug and/drug metabolites excreted in urine, faeces or bile
54
pKa
pH at which 50% of the drug is ionized and 50% is unionised
HH equation
pKa = pH + log(AH/A)
55
What does lower pKa and higher Ka mean?
Stronger acid (lower pH)
56
pH trapping
Weak bases accumulate in compartments with low pH (+ reverse)
57
Apparent vol of distribution (Vd)
Vd: extent to which a drug partitions between the plasma and tissue compartments
- Low Vd = drugs retained in vascular compartments
- High Vd = drugs retained in non-vascular compartments – adipose, muscle etc.
58
Effect of albumin on Vd
- Reduces the ability of the drug for diffusion to target organ
- May also reduce transport of the drug to non-vascular components
59
Factors influencing drug elim
Abs>elim before optimum conc (first order)
| Abs
60
Clearance def
An expression of the elimination of a drug from the body - the volume of blood removed of a drug per unit time
CLR, CLH, CHO, CLT
61
Equation for CL
CL = rate of drug elimination/[D] plasma
62
Steady state
When rate of drug admin=rate of elim (R0=RE)
63
Elim half-life equation
t½ = (0.693 x Vd)/CL
64
Gm + vs gm -
Gm + thick peptidoglycan, purple
| Gm- thin peptidoglycan, pink
65
What are biofilms more resistant to?
Antimicrobials
66
Aerobes vs anaerobes
- **Aerobic:** grow in oxygen
- **Obligate aerobes:** require oxygen
- **Obligate anaerobes:** killed by oxygen
- **Facultative anaerobes:** tolerate oxygen
67
Coagulase vs haemolysis
Coag - stah aureus (+) vs - staph
| Haemolysis - diff between strep
68
Why do gm - sepsis patients deteriorate so quickly?
Gram-negative sepsis get very unwell very quickly due to endotoxin released when Gram-negative bacteria die
69
Process of fever
1. Antigen/LPS interacts with macrophages
2. Macrophages release cytokines into bloodstream
3. Cytokines travel to anterior hypothalamus
4. Prostaglandin E released - increases body’s thermal set point
5. Body perceives it as cold - starts to ‘shiver’
6. FEVER
70
Examples of each bac type
Gm- cocci - neisseria men and gonn
| Gm+ cocci - strep, GAS, staph epi and aureus, enterococcus, clostridium
71
Symmetry of viruses
- **Icosahedral symmetry:** virus consists of repeated subunits that make up equilateral triangles arranged in a symmetrical fashion
- **Helical symmetry:** made up of a single repeated unit
72
Process of viral infection
```
Replication
Attachment
ENtry
Uncoating
NA and protein synth
Assembly
Release
```
73
How do they become resistant?
Genetic mutation
| Transfer of bac DNA (transformation, conjugation, transduction)
74
Empirical antibios
- Staph aureus: flucloxacillin IV
- Staph epidermidis: vancomycin IV
- Strep pyrogenes: doxycycline
- Gram negatives: clindamycin
- Anaerobes: metronidazole, cotriomazol
75
Mechs of resistance to antibiotics
Altered binding site
Destruction of antibio (ESBLs*****)
Incr efflux
76
Bacteriostatic vs cidal
- **Bacteriostatic:** inhibit growth of bacteria
| - **Bactericidal:** kill bacteria
77
ANtibiotics acting on cell wall
Penicillins (fluclox, amox)
Cephalosporins (cefaclor, cefadroxil)
Glycopeptides (vancomycin)
78
Antibios inhibiting protein synth
Macrolides (erythro, azithro)
Aminoglycocides (gentamicin)
Clindamycin, tetracycline, cholarmphenicol
79
Antibios on bac DNA
Metronidazole
Trimethoprim
Fluoroquinolones - c diff (ciprofloxacin, levofloxacin)
80
Cell cycle
G1
S (DNA synth)
G2
M
81
SNPs and CVNs
SNP - single nucleotide polymorph, most have no effect
| CVN - extra/missing stretches of DNA; deletions or duplications
82
Unbalanced chromosome rearragement
- Extra or missing chromosomal material, usually 1 or 3 copies of gene
- Causes major developmental problems
83
Aneuploidy
Whole extra/ missing
X chromosome is better tolerated
Monosomy - lack of one
Trisomy - 3 copies (trisomy 21 - downs)
84
Turner's
Female w only one X
85
Specific aneuplodies
- **47XY +21** (trisomy 21) - Down’s syndrome
- **47 XY +14** (trisomy 14) - miscarriage
- **47 XY +18** - Edward syndrome, trisomy 18
- **45 X** - Turner syndrome
- **47 XXY** - Klinefelter syndrome
86
Somatic mosaicism
Two genetically distinct populations of cells within an individual, derived from a post-zygotic mutation
87
Robertsonian vs reciprocal
Rob
- Two acrocentric chromosomes stuck end to end
- Increased risk of trisomy in pregnancy
Recip
- Two broken off chromosome pieces of non-homologous chromosomes are exchanged
88
Gene analysis tests
```
aCGH - 1st line, detects missing/dup chroms
FISH - fluorescent probs
PCR - amp small piece
Whole genome seq - all exons
Genetic filter
```
89
Types of mutations
Missense (change to single AA, most likely activate oncogene)
Change to AA seq
Insertion/deletion (frameshift)
Promoter and splice site change
90
How is mitochondrial disease transmitted?
Mitochondrial DNA is transmitted maternally, in the ovum
90
How is mitochondrial disease transmitted?
Mitochondrial DNA is transmitted maternally, in the ovum
91
DNA methylation
- Usually occurs on cytosine bases just before guanine bases
| - Prevents transcription (leads to modification of histones)
92
How are proto-oncogenes activated?
```
Point mutation (BRAF)
AMplification (HER2)
Translocation (Philadelphia)
```
93
Lynch syndrome
Hereditary form of cancer due to mutation in mismatch repair gene
94
Incidence vs prevalence
- **Incidence rate:** (number of NEW cases of a disease occurring in a population during a specific time period/number of persons exposed to the risk of developing the disease during that time period) x 1000
- **Prevalence rate:** (number of cases of a disease present in a population at a given time/number of persons at risk of the disease at that point in time) x 1000
95
Cytokines
- Interferons released by virally infected cells signal to neighbouring uninfected cells:
- Destroy RNA and reduce protein synthesis
- Undergo apoptosis
96
Macrophages and mast cells
Macro - Phagocytose bacteria
| Mast - deal w pathogens too large for phagocytosis
97
Transendothelial migration
Recruitment of neutrophils to the site of infection/damage during acute inflammation
98
Killing pathogen mechanisms
- **Phagocytosis:** phagolysosomal killing (like macrophages) via production of reaction oxygen species (ROS)
- **Degranulation:** release of anti-bacterial granules
- **NETs:** release of a net-like structure that traps pathogens, leading to phagocytosis
99
Pinocytosis
ingestion of fluid of surrounding cells
100
Acute phase proteins
- C3 - involved in complement
- CRP - activates complement via classical pathway (incr in inflam)
- MBL - activates complement via MBL pathway
101
Classical pathway activated by which Ig
IgM and IgG
102
What signals do B cells require to become active and proliferate?
Antigen
| Helpr signals
103
T cell types
- **CD4+ Helper T cells:** activate B cells & stimulate production of memory B cells
- **CD8+ Killer T cells:** kill infected cells via perforin/granzymes/granulysin
- **Regulatory T cells:** lymphocyte suppression
- **Memory T cells:** involved in the adaptive immune response
104
Class 1 and 2 MHC
- **Class I MHC:** expressed on all nucleated cells, present peptide antigens to CD8+ killer T cells
- **Class II MHC:** expressed only on antigen presenting cells (e.g. dendrites, macrophages), present peptide antigens to CD4+ helper T cells
105
CD4+ cells and CD8+ cells diff into which cells?
**CD4+ T cells → T helper cells**
| CD8+ T cells → CTLs (TC cells)
106
Fick's law of diffusion
- ↑ concentration gradient (𝝙C) = ↑ rate of diffusion (Q)
- ↑ surface area of membrane (A) = ↑ rate of diffusion
- ↑ lipid solubility = ↑ rate of diffusion
- ↑ molecular weight of substance = ↓ rate of diffusion
- ↑ distance (thickness) = ↓ rate of diffusion
107
Fick's law of diffusion
- ↑ concentration gradient (𝝙C) = ↑ rate of diffusion (Q)
- ↑ surface area of membrane (A) = ↑ rate of diffusion
- ↑ lipid solubility = ↑ rate of diffusion
- ↑ molecular weight of substance = ↓ rate of diffusion
- ↑ distance (thickness) = ↓ rate of diffusion
108
Secondary active transport
- **Symport:** solute and Na+ move in the same directio
| - **Antiport:** solute and Na+ move in opposite directions (Na+ in, solute out)
109
Exo vs endocytosis
- **Exocytosis:** vesicle fuses with plasma membrane, releasing its contents to the ECF
- **Endocytosis:** 'pinching off’ of membrane to engulf substance
110
Exer vs endergonic reactions
Exer - Total free energy of products is less than total free energy of reactants
Ender - Total free energy of products is more than total free energy of reactants
111
When does pH = pKa?
When the concentration of acid is equal to the concentration of the conjugate base
112
Structures of RNA and DNA
- **Nucleoside:** base and 5 carbon sugar
- **Nucleotide:** nucleoside and phosphate group
- **Purines:** adenine and guanine
- **Pyrimidines:** cytosine, thymine, uracil
- **Phosphodiester bonds:** form between 3’ OH group and 5’ triphosphate, link nucleotides
113
How is DNA synthesised?
5->3 direction
114
Stages of translation
Initiation
Elongation
Peptide bond formation and translocation
Termination
115
Apo vs holoenzyme
- **Apoenzyme:** enzyme without cofactor (metal ion req)
| - **Holoenzyme:** enzyme with cofactor
116
Michaelis-Menten Kinetics
- **S:** solute concentration
- **V0:** initial rate (velocity) of reaction
- **VMAX:** the maximum rate of reaction when all enzyme active sites are saturated with substrate velocity
- **Km** (Michaelis constant): the substrate concentration that gives half maximal velocity
117
Km = ?
```
Km = [S] at 0.5(VMAX)
Km = (k-1+k2)k1
```
Low Km (only need little substrate to work at half max velocity and vice versa)
118
k1, k-1, k2
- k1 = forward rate for enzyme association with substrate
- k-1 = backwards rate for enzyme dissociation with substrate
- k2 = forward rate of enzyme conversion from energy to product
119
Control points of glycolysis
Phosphofructokinase
Glyceraldehyde 3-phosphate
Pyruvate kinase
H+
120
Warburg effect
Cancer cells produce energy by high rate of glucose metabolism to lactate - anaerobic glycolysis
(low Km hexokinase)
121
How is NAD regenerated?
Krebs cycle
122
Stages of TCA cycle (krebs)
1. pyruvate enter
2. pyruvate -> acetyl coA
3. acetyl coA + oxaloacetate -> citrate
4. citrate decarboxylated twice (yields 2 CO2)
5. 4 ox reactions to yield NADH, H, FADh
6. GTP formed
7. oxaloacetate reformed
123
What is generated from each acetyl-coA?
- 3 NADH + H+
- 1 FADH2
- 1 GTP
- 2 CO2
124
Per glucose how many NADH etc are yielded?
- 10 NADH and 10 H+
- 2 FADH2
(eac one has 2 high energy electrons for ETC/ox phosph)
125
Process of oxidative phosph
1. resp chain where electrons are handed down incr pos potentials (O2 is final accepto -> H2O)
2. coupled to H transport from matrix
3. 4 resp complexes pump H into IM space
4. H flows back into matrix through ATP synthase
126
Inhibition of ox phosph
Cyanide
Azide
CO
127
How many ATP?
Net 30-32 from ETC
128
Types of plasia
Dys - abnorm growing w/o stm
Meta - reversible change between cell types
Hyper - incr in number from stim
129
Hallmarks of cancer
- Resisting apoptosis
- Sustained proliferative signaling
- Evading growth suppressors
- Activating invasion and metastasis
- Inducing angiogenesis
130
Stage vs grade in caner
Stage - how far
| Grade - how bad
131
Mechs of disease mnemonic
VINDICATE
132
Types of necrosis
Coag - MI
Liquefactive - Bac/fung/brain
Caseous - TB
133
Cell changes in resp to injury
```
Stasis
Margination
Rolling
Adhesions
Transendo migration
```
134
What are the 4C antibiotics most likely to cause C. diff?
Co-amoxiclave
Clindamycin
Ciprofloxacin
Cefuroxime
135
Which immunoglobulin is transported across placenta for foetal immune protection?
IgG
136
Group A strep shows what type of haemolysis?
Complete haemolysis
137
Function of oligodendrocytes
Secretion of insulating material in CNS
